The Challenging World of Simple Inorganic Rings: Revisiting Roesky's Ketone and Roesky's Sulfoxide.

The surprising differences between the experimental solid-state and calculated gas-phase structures of 5-oxo-1,3,2,4-dithiadiazole (Roesky's ketone, 1) and 1-oxo-1,2,4,3,5-trithiadiazole (Roesky's sulfoxide, 2), identified and studied in a series of papers published between 2004 and 2010 but then never satisfactorily explained, have been revisited, making use of the more advanced computational possibilities currently available. The previous calculations' considerable overestimations of the C-S and S-S bond lengths in 1 and 2, respectively, have been partly explained based on the results of periodic calculations and the application of Valence Bond (VB) Theory. In the case of 1, the crystal environment appears to stabilize a structure with a highly polarized C=O bond, which features a C-S bond with considerable double-bond character - an effect which does not exist for the isolated molecule - explaining the much shorter bond in the solid state. For 2, a similar conclusion can be drawn for the S-S distance. For both compounds, though, packing effects are not the sole source of the differences: the inability of Density Functional Theory (DFT) to properly deal with the electronic structures of these apparently simple main-group systems remains a contributing factor.

Investigating the Linear Response Function under Approximations Following the Coupled-Perturbed Approach for Atoms and Molecules.

The linear response kernel also referred to as linear response function (LRF) in the framework of conceptual density functional theory has gained tremendous success in time-dependent density functional theory. Comparatively less attention has been devoted to the LRF from a chemical reactivity perspective in its time- or frequency-independent context, although it has recently been used to qualitatively describe electron delocalization, (anti-)aromaticity, inductive and mesomeric effects, etc. Despite these successes, which were obtained by approximating the LRF using the independent particle approximation deriving from a coupled-perturbed Kohn-Sham computation, the robustness of this LRF approach needs to be assessed. In this work, we compute the LRF at four levels of approximation (independent particle approximation, random phase approximation, Hartree-Fock approximation, and the (exact) DFT (density functional theory) expression) using functionals from the first four rungs of Jacob's ladder of exchange-correlation energy functionals. To scrutinize the impact of these approximations, new visualization strategies are discussed and systematized. The overall conclusion is that the independent particle approximation yields qualitatively correct results (ergo previous conceptual applications of the LRF are trustworthy), but for quantitative results, LRF expressions including coulomb and exchange(-correlation) terms should be included. With respect to functionals, density-gradient contributions to the exchange-correlation kernel are less than 10% and may be omitted safely where that is preferable computationally.

An Overview of Self-Consistent Field Calculations Within Finite Basis Sets.

A uniform derivation of the self-consistent field equations in a finite basis set is presented. Both restricted and unrestricted Hartree-Fock (HF) theory as well as various density functional approximations are considered. The unitary invariance of the HF and density functional models is discussed, paving the way for the use of localized molecular orbitals. The self-consistent field equations are derived in a non-orthogonal basis set, and their solution is discussed also in the presence of linear dependencies in the basis. It is argued why iterative diagonalization of the Kohn-Sham-Fock matrix leads to the minimization of the total energy. Alternative methods for the solution of the self-consistent field equations via direct minimization as well as stability analysis are briefly discussed. Explicit expressions are given for the contributions to the Kohn-Sham-Fock matrix up to meta-GGA functionals. Range-separated hybrids and non-local correlation functionals are summarily reviewed.

QCMS2 as a new method for providing insight into peptide fragmentation: The influence of the side-chain and inter-side-chain interactions.

The identification of peptides and proteins from tandem mass spectra is a difficult task and multiple tools have been developed to aid this identification. We present a new method called quantum chemical mass spectrometry for materials science (QCMS2 ), which is based on quantum chemical calculations of bond orders, reaction, and transition-state energies at the DFT/B3LYP/6-311+G* level of theory. The method was used to describe the fragmentation pathways of five X-His-Ser tripeptides with X = Asn, Asp, Glu, Ser, and Trp, thereby focusing on the influence of the side chain and inter-side-chain interactions on the fragmentation. The main features in the mass spectra of the five tripeptides were correctly reproduced, and a number of fragments were assigned to fragmentations involving the side chain and the influence of inter-side-chain interactions. Product ion spectra were recorded to evaluate the capabilities and limitations of QCMS2 and a number of conventional tools.

Exploring chemical space with alchemical derivatives: alchemical transformations of H through Ar and their ions as a proof of concept.

Alchemical derivatives have been used in recent years to obtain essentially qualitative information about transformations in which the number of electrons is unchanged. Within the context of Conceptual DFT, we present a systematic approach for combining changes in both the number of electrons and the nuclear charge so that for example one can navigate from one neutral atom to another. A general formalism is presented for transformations involving changes both in or , where Parr's parabolic approach for the dependence is considered as one particular case and the ensemble description in the 0 K limit as the second case. The B3LYP functional in its CAMB3LYP version combined with the aug-cc-pCVQZ basis has been chosen to perform Coupled Perturbed Kohn Sham calculations of the alchemical derivatives. The monotonic behaviour of the alchemical potential is scrutinised. The order of magnitude analysis of the derivatives preludes convergence at third order. These results are injected in two strategies for obtaining transmutation energies from neutral atoms to a neighbouring neutral atom: one road moving along the diagonal, the other one walking along a pure alchemical road after ionisation or electron attachment. Roads involving the anion of the reference atom are much less successful than those involving its cation. The transmutation energy for the cationic pathway displays chemical accuracy when the procedure is carried at third order in . The difficulties inherent to an accurate description of the anion and its response functions are responsible for the shortcomings along the anionic paths. As a direct application Ionization Energies (IE) and Electron Affinities (EA) are evaluated showing an almost perfect agreement with the direct evaluation and a difference with experimental values less than 0.5 eV for the IE. For the first EA reasonable agreement is obtained with direct and experimental values whereas the second EAs for atoms with stable mono-anions show a remarkable agreement with literature data. Besides proof of concept that with the information content of an atom one can get accurate energetics of its neighbours, the results indicate that alchemical derivatives are capable to yield quantitative information when navigating through Chemical Compound Space.

Ab initio study on the six lowest energy conformers of iso-octane: conformational stability, barriers to internal rotation, natural bond orbital and first-order hyperpolarizability analyses, UV and NMR predictions, spectral temperature sensitivity, and scaled vibrational assignment.

In this paper, we present the quantum electronic study of iso-octane, based on MP2 and B3LYP methods using the 6-311++G(d,p) basis set. In addition to conformational stability and internal rotation barriers studies, the delocalization energies associated with the internal charge transfer (ICT) within each of the six lowest energy conformers were evaluated using NBO analysis. With the aim to differentiate even more between these conformers, the energy gap between HOMO and LUMO orbitals, chemical softness, and first-order hyperpolarizability (nonlinear optics property) were evaluated. Similarly, their spectral behavior was investigated at different levels; the ultraviolet (UV) absorption bands were assigned using molecular orbitals data obtained by TD-B3LYP calculations with 6-311++G(d,p) basis set, while carbon 13C NMR and proton 1H signal peaks were assigned using the GIAO-B3LYP/6-311++G(d,p) method. In addition, the normal mode calculations of the most and least stable conformers using a scaled force field in terms of nonredundant local symmetry coordinates were carried out to approach the vibrational spectra temperature dependency.

Molecular structure, FT-IR, FT-Raman, NBO, HOMO and LUMO, MEP, NLO and molecular docking study of 2-[(E)-2-(2-bromophenyl)ethenyl]quinoline-6-carboxylic acid.

The optimized molecular structure, vibrational frequencies, corresponding vibrational assignments of 2-[(E)-2-(2-bromophenyl)ethenyl]quinoline-6-carboxylic acid have been investigated experimentally and theoretically using Gaussian09 software package. Potential energy distribution of the normal modes of vibrations was done using GAR2PED program. (1)H NMR chemical shifts calculations were carried out by using B3LYP functional with SDD basis set. The HOMO and LUMO analysis is used to determine the charge transfer within the molecule. The stability of the molecule arising from hyper-conjugative interaction and charge delocalization has been analyzed using NBO analysis. MEP was performed by the DFT method and the predicted infrared intensities and Raman activities have also been reported. The calculated geometrical parameters are in agreement with that of similar derivatives. The title compound forms a stable complex with PknB as is evident from the binding affinity values and the molecular docking results suggest that the compound might exhibit inhibitory activity against PknB and this may result in development of new anti-tuberculostic agents.

Vibrational spectroscopic and molecular docking study of (2E)-N-(4-chloro-2-oxo-1,2-dihydroquinolin-3-yl)-3-phenylprop-2-enamide.

FT-IR and FT-Raman spectra of (2E)-N-(4-chloro-2-oxo-1,2-dihydroquinolin-3-yl)-3-phenylprop-2-enamide were recorded and analyzed experimentally and theoretically. The synthesis, (1)H NMR and PES scan results are also discussed. Nonlinear optical behavior of the examined molecule was investigated by the determination of first hyperpolarizability. The calculated HOMO and LUMO energies show the chemical activity of the molecule. The stability of the molecule arising from hyper-conjugative interaction and charge delocalization has been analyzed using NBO analysis. From the MEP it is evident that the negative charge covers the carbonyl group and the positive region is over the NH group. The calculated geometrical parameters (SDD) are in agreement with that of similar derivatives. Molecular docking simulations against targets from Mycobacterium tuberculosis are reported and the results suggest that the compound might exhibit inhibitory activity against PknB.

Hirshfeld-based intrinsic polarizability density representations as a tool to analyze molecular polarizability.

In this work, a general scheme to visualize polarizability density distributions is proposed and implemented in a Hirshfeld-based partitioning scheme. This allows us to obtain easy-to-interpret pictorial representations of both total and intrinsic polarizabilities where each point of the density is formed by the contribution of any atom or group of atoms in the molecule. In addition, the procedure used here permits the possibility of removing the size dependence of the electric-dipole polarizability. Such a development opens new horizons in exploring new applications for the analysis of the molecular polarizability tensor. For instance, this visualization shows which atoms or regions are more polarizable distinguishing, moreover, the fine structure of atoms affected by the vicinity, and might extend the dipole polarizability as a tool for aromaticity studies in polycyclic aromatic hydrocarbons. Additionally, this approach can serve us to assess the methods performance in describing the interaction of electric fields with a molecule and local electron correlation effects in intrinsic polarizabilities.

Vibrational spectra, HOMO, LUMO, NBO, MEP analysis and molecular docking study of 2,2-diphenyl-4-(piperidin-1-yl)butanamide.

The Fourier-Transform Infrared and Fourier-Transform Raman spectra of 2,2-diphenyl-4-(piperidin-1-yl)butanamide were recorded in the region 4000-400 cm(-1) and 4000-0 cm(-1). The vibrational wavenumbers are computed using HF and DFT methods. The complete vibrational assignments were performed on the basis of potential energy distribution using GAR2PED program. The geometrical parameters of the title compound are in agreement with the XRD data. From the MEP study, the negative electrostatic potential regions are mainly localized of carbonyl group and are possible sites for electrophilic attack and the positive regions are localized all the rings, indicating possible sites for nucleophilic attack. Stability of the molecule arising from hyper-conjugative interaction and charge delocalization has been analyzed using natural bond orbital analysis. The calculated HOMO and LUMO energies also confirm that charge transfer occurs within the molecule. PASS analysis of the title compound predicts among other activities, antidyskinetic activity. Molecular docking results draw us to the conclusion that the compound might exhibit inhibitory activity against adenosine A2A and may act as antidyskinetic agent.

Vibrational spectroscopic studies and molecular docking study of 2-[(E)-2-phenylethenyl]quinoline-5-carboxylic acid.

FT-IR and FT-Raman spectra of 2-[(E)-2-phenylethenyl]quinoline-5-carboxylic acid were recorded and obtained and analyzed. The vibrational wavenumbers were computed using DFT quantum chemical calculations. The geometrical parameters (SDD) of the title compound are in agreement with that of similar derivatives. Stability of the molecule arising from the hyper conjugative interactions, charge delocalization has been analyzed using natural bond orbital analysis. From the natural and Mulliken charges, it can be concluded that electrophilic substitution of the quinoline scaffold is more preferred than nucleophilic substitution. From the MEP map it is evident that the negative regions are mainly localized over the carbonyl group and are possible sites for electrophilic attack. The title compound forms a stable complex with PknB as is evident from the binding affinity values and the molecular docking study suggests that the compound might exhibit inhibitory activity against PknB.

Spectroscopic investigation (FT-IR and FT-Raman), vibrational assignments, HOMO-LUMO, NBO, MEP analysis and molecular docking study of 2-[(4-chlorobenzyl)sulfanyl]-4-(2-methylpropyl)-6-(phenylsulfanyl)-pyrimidine-5-carbonitrile, a potential chemotherapeutic agent.

Vibrational spectral analysis of 2-[(4-chlorobenzyl)sulfanyl]-4-(2-methylpropyl)-6-(phenylsulfanyl)-pyrimidine-5-carbonitrile was carried out using FT-IR and FT-Raman spectroscopic techniques. The equilibrium geometry and vibrational wave numbers have been computed using density functional B3LYP method with 6-311++G(d,p)(5D,7F) as basis set. Stability of the molecule arising from hyper conjugative interactions, charge delocalization has been analyzed using NBO analysis. The nonlinear optical behavior of the title compound is also theoretically predicted. From the MEP, it is evident that the negative charge covers the C≡N group and the positive region is over the phenyl and the pyrimidine rings. From the potential energy scan it is clear that the lone pairs of the sulfur atom prefer to point away from the pyrimidine ring and the C≡N group resulting with two possible minimum conformations at the N4C8S1C25 angle equal nearly 0° or 150°. Molecular docking results suggest that the compound might exhibit inhibitory activity against GPb and may act as potential anti-diabetic compound.

Molecular structure, FT-IR, vibrational assignments, HOMO-LUMO, MEP, NBO analysis and molecular docking study of ethyl-6-(4-chlorophenyl)-4-(4-fluorophenyl)-2-oxocyclohex-3-ene-1-carboxylate.

The optimized molecular structure, vibrational frequencies, corresponding vibrational assignments of ethyl-6-(4-chlorophenyl)-4-(4-fluoro-phenyl)-2-oxocyclohex-3-ene-1-carboxylate have been investigated experimentally and theoretically using Gaussian09 software. The title compound was optimized using the HF and DFT levels of theory. The geometrical parameters are in agreement with the XRD data. The stability of the molecule has been analyzed by NBO analysis. The HOMO and LUMO analysis is used to determine the charge transfer within the molecule. Molecular electrostatic potential was performed by the DFT method. As can be seen from the MEP map of the title compound, regions having the negative potential are over the electro negative atoms, the region having the positive potential are over the phenyl rings and the remaining species are surrounded by zero potential. First hyperpolarizability is calculated in order to find its role in non linear optics. The title compound binds at the active sites of both CypD and ß-secretase and the molecular docking results draw the conclusion that the compound might exhibit ß-secretase inhibitory activity which could be utilized for development of new anti-alzheimeric drugs with mild CypD inhibitory activity.

FT-IR, NBO, HOMO-LUMO, MEP analysis and molecular docking study of 1-[3-(4-Fluorophenyl)-5-phenyl-4,5-dihydro-1H-pyrazol-1-yl]ethanone.

The optimized molecular structure, vibrational frequencies, corresponding vibrational assignments of 1-[3-(4-fluorophenyl)-5-phenyl-4,5-dihydro-1H-pyrazol-1-yl]ethanone have been investigated experimentally and theoretically. The geometrical parameters are in agreement with XRD data. The stability of the molecule arising from hyper-conjugative interaction and charge delocalization has been analyzed using NBO analysis. The HOMO and LUMO analysis is used to determine the charge transfer within the molecule. From the MEP it is evident that the negative charge covers the carbonyl group and the positive region is over the remaining groups. The more electronegativity in the carbonyl group makes it the most reactive part in the molecule. First hyperpolarizability is calculated in order to find its role in nonlinear optics. From the molecular docking studies, it is evident that the fluorine atom attached to benzene ring and ethanone attached to the pyrazoline ring are crucial for binding and the compound might exhibit inhibitory activity against TPII and may act as anti-neoplastic agent.

Molecular structure, FT-IR, vibrational assignments, HOMO-LUMO analysis and molecular docking study of 1-[5-(4-Bromophenyl)-3-(4-fluorophenyl)-4,5-dihydro-1H-pyrazol-1-yl]ethanone.

The optimized molecular structure, vibrational frequencies, corresponding vibrational assignments of 1-[5-(4-bromophenyl)-3-(4-fluorophenyl)-4,5-dihydro-1H-pyrazol-1-yl]ethanone have been investigated experimentally and theoretically using Gaussian09 software package. The title compound was optimized using the HF/6-31G(d) (6D, 7F), B3LYP/6-31G (6D, 7F) and B3LYP/6-311++G(d,p) (5D, 7F) calculations. The B3LYP/6-311++G(d,p) (5D, 7F) results and in agreement with experimental infrared bands. The geometrical parameters are in agreement with XRD data. The stability of the molecule arising from hyper-conjugative interaction and charge delocalization has been analyzed using NBO analysis. The HOMO and LUMO analysis is used to determine the charge transfer within the molecule. Molecular electrostatic potential was also performed. From the MEP it is evident that the negative charge covers the C=O group and the positive region is over the rings. First hyperpolarizability is calculated in order to find its role in nonlinear optics. Molecular docking studies suggest that the compound might exhibit inhibitory activity against TPII and may act as anti-neoplastic agent.

Spectroscopic investigation (FT-IR, FT-Raman), HOMO-LUMO, NBO analysis and molecular docking study of 2-[(4-chlorobenzyl)sulfanyl]-4-(2-methylpropyl)-6-[3-trifluoromethyl)-anilino]pyrimidine-5-carbonitrile, a potential chemotherapeutic agent.

FT-IR and FT-Raman spectra of 2-[(4-chlorobenzyl)sulfanyl]-4-(2-methylpropyl)-6-[3-trifluoromethyl)-anilino]pyrimidine-5-carbonitrile were recorded and analyzed. The vibrational wave numbers were computed using DFT quantum chemical calculations. The data obtained from wave number calculations are used to assign vibrational bands obtained in infrared and Raman spectra. Potential energy distribution was done using GAR2PED program. The NH stretching wave number is red shifted by 102 cm(-1) in IR from the computed wave number, which indicates the weakening of the NH bond. The geometrical parameters (DFT) of the title compound are in agreement with the XRD results. NBO analysis, HOMO-LUMO, first hyperpolarizability and molecular electrostatic potential results are also reported. From the MEP map it is evident that the negative electrostatic potential regions are mainly localized over the CN and CF3 groups and are possible sites for electrophilic attack and positive regions are localized around NH group, indicating possible sites for nucleophilic attack. The preliminary docking results suggest that the title compound might exhibit inhibitory activity against GPb and may act as a potential anti-diabetic compound.

Theoretical study of the adsorption of aromatic units on carbon allotropes including explicit (empirical) DFT dispersion corrections and implicitly dispersion-corrected functionals: the pyridine case.

The suitability of implicitly dispersion-corrected functionals, namely the M06-2X, for the determination of interaction energies and electron polarization densities in adsorption studies of aromatic molecules on carbon allotropes surfaces is analysed by comparing the results with those obtained using explicit dispersion through Grimme's empirical corrections. Several models of increasing size for the graphene sheet together with one-dimensional curved carbon structures, (5,5), (6,6) and (7,7) armchair single-walled nanotubes, and two-dimensional curved carbon structures, C60 fullerene, have been considered as substrates in this work, whereas pyridine has been chosen as an example for the adsorbed aromatic molecule. Comparison with recent experimental estimations of the adsorption energy and calculations using periodic boundary conditions on a supercell of 72 carbon atoms indicates that a finite model containing ninety six carbon atoms (C96) approaches quite well the adsorption on a graphene sheet. Analysis of the interaction energy components reveals that the M06-2X functional accounts for most of the dispersion energy implicitly, followed far by wB97X and B3LYP, whereas B97 and BLYP do not differ too much from HF. It has been found that M06-2X corrects only the energy component associated to dispersion and leaves the rest, electrostatic, Pauli and induction "unaltered" with respect to the other DFT functionals investigated. Moreover, only the M06-2X functional reflects the effect of dispersion on the electron polarization density, whereas for the remaining functionals the polarization density does not differ too much from the HF density. This makes the former functional more suitable a priori for the calculation of electron density related properties in these adsorption complexes.

Spectroscopic (FT-IR, FT-Raman), first order hyperpolarizability, NBO analysis, HOMO and LUMO analysis of 5-tert-Butyl-6-chloro-N-[(4-(trifluoromethyl)phenyl]pyrazine-2-carboxamide.

The optimized molecular structure, vibrational frequencies, corresponding vibrational assignments of 5-tert-Butyl-6-chloro-N-[(4-(trifluoromethyl)phenyl]pyrazine-2-carboxamide have been investigated experimentally and theoretically using Gaussian09 software package. Potential energy distribution of normal modes of vibrations was done using GAR2PED program. The HOMO and LUMO analysis is used to determine the charge transfer within the molecule. The stability of the molecule arising from hyper-conjugative interaction and charge delocalization has been analyzed using NBO analysis. From the NBO analysis it is evident that the increased electron density at the nitrogen, carbon atoms leads to the elongation of respective bond length and a lowering of the corresponding stretching wave number. The calculated geometrical parameters are in agreement with that of similar derivatives. The calculated first hyperpolarizability is high and the calculated data suggest an extended π-electron delocalization over the pyrazine ring and carboxamide moiety which is responsible for the nonlinearity of the molecule.

Vibrational spectroscopic studies and molecular docking of 10,10-Dimethylanthrone.

FT-IR and FT-Raman spectra of 10,10-Dimethylanthrone were recorded and analyzed. The vibrational wavenumbers were computed using DFT quantum chemical calculations. The data obtained from wavenumber calculations are used to assign vibrational bands obtained experimentally. In its most stable form, the title compound maintains C2v symmetry as determined by XRD results, where both methyl groups are staggered with respect to the corresponding C23-C24 and C23-C28 bonds. The geometrical parameters (B3LYP/6-311++G(d,p)(5D,7F)) of the title compound are in agreement with the XRD results. The calculated HOMO and LUMO energies allow the calculations of atomic and molecular properties and they also showed that charge transfer occurs in the molecule. A detailed molecular picture of the title compound and its interactions were obtained from NBO analysis. As seen from the MEP map, negative potential regions are localized over the carbonyl group and are possible sites for electrophilic attack. The title compound, 10,10-Dimethylanthrone forms a stable complex with human topoisomerase-II as is evident from the ligand-receptor interactions and show appreciable antineoplastic activity.

Vibrational spectroscopic (FT-IR and FT-Raman) studies, HOMO-LUMO, NBO analysis and MEP of 6-methyl-1-({[(2E)-2-methyl-3-phenyl-prop-2-en-1-yl]oxy}methyl)-1,2,3,4-tetra-hydroquinazoline-2,4-dione, a potential chemotherapeutic agent, using density functional methods.

6-Methyl-1-({[(2E)-2-methyl-3-phenyl-prop-2-en-1-yl]oxy}methyl)-1,2,3,4-tetra-hydro quinazoline-2,4-dione was prepared via treatment of silylated 6-methylquinazoline-2,4-dione with bis-[(E)-2-methyl-3-phenylallyloxy]methane. FT-IR and FT-Raman spectra were recorded and analyzed. The vibrational wavenumbers were computed using DFT methods and are assigned with the help of potential energy distribution method. The first hyperpolarizability, infrared intensities and Raman activities also reported. The geometrical parameters of the title compound obtained from XRD studies are in agreement with the calculated (B3LYP) values. The stability of the molecule arising from hyper-conjugative interaction and charge delocalization has been analyzed using NBO analysis. The HOMO and LUMO analysis are used to determine the charge transfer within the molecule. MEP was performed by the B3LYP method and from the MEP it is evident that the negative charge covers the CO group and the positive region is over the phenyl ring and NH group.